Lakhani et al., IJPSR, 2015; Vol. 6(5): 1826-36.

E-ISSN: 0975-8232; P-ISSN: 2320-5148

IJPSR (2015), Vol. 6, Issue 5 (Review Article)

Received on 12 June, 2014; received in revised form, 17 November, 2014; accepted, 06 January, 2015; published 01 May, 2015

TRANSDERMAL PATCHES: PHYSIOCHEMICAL AND IN-VITRO EVALUATION METHODS

Prit Lakhani*, Rishabh Bahl and Piyush Bafna
Department of Pharmacy, Bits-Pilani, Jawahar Nagar, Shameerpet Mandal, Hyderabad, Telangana, India
Keywords: ABSTRACT: Various drugs are available these days, which may either require
long term administration via multiple doses or may be susceptible to enzymes
Transdermal route, and first pass-metabolism or all the above. One way to administer such drugs is
In-vitro, chemical properties, through the transdermal route. After a transdermal delivery system is designed, it
first pass-metabolism Physio- is important to evaluate it for various essential parameters that help us determine
chemically, how effective it is, i.e. its physiochemical parameters, which describe the
Correspondence to Author: physical and some of the chemical properties of the patch and it’s in-vitro
Prit Lakhani parameters, which would mimic how the patch would behave on exposure to real
Department of Pharmacy, Bits-Pilani, Jawahar time conditions On the body. This article briefly reviews the ideal characters for
Nagar, Shameerpet Mandal, Hyderabad - choosing this mode of drug delivery, its advantages and provides an in-depth
500078, Telangana, India analysis of the techniques used to physio-chemically evaluate the delivery
system’s important parameters and also the conditions that help understand the
E-mail:
h2013146076@hyderabad.bits-pilani.ac.in systems behavior in a real time scenario.

INTRODUCTION: Transdermal systems have Biopharmaceutical Parameters for selection of an

evolved a lot over the decade. Maintenance of drug
level above minimum effective concentration has
always been considered as a superior mode of drug
delivery. It is always desirable to bypass first pass
metabolism and also to maintain constant,
prolonged, and effective drug concentration levels
in the plasma. Using transdermal systems has been
highly advantageous in mimicking above state 2-6.
The transdermal systems have various advantages
which led to its exploitation As a drug delivery
system and vast number of advancements have
been observed over time. Various advantages are
listed in the flow chart (Fig). Listed below are the
biopharmaceutical parameters for the selection of
an ideal drug for transdermal drug delivery.
QUICK RESPONSE CODE
DOI:
10.13040/IJPSR.0975-8232.6(5). 1826-36
Article can be accessed online on:
www.ijpsr.com
DOI link: http://dx.doi.org/10.13040/IJPSR.0975-8232.6(5). 1826-36
ideal drug for transdermal drug delivery 3, 4:
 Dose: Should be low (generally
<20mg/day).
 Elimination Half-life of drug (hr.): ≤10.
 Molecular weight: < 500-400 Daltons.
 Partition Coefficient: Log P (Octanol-
Water) should be in the range of 1 to 3.
 Skin permeability: >0.5 X 10-3 cm/hr.
 The drug should be non-irritating and non-
sensitizing.
 Drug with low oral bioavailability.
 Drug with low therapeutic index.
Transdermal patches are designed to control the
drug delivery through the skin, resulting in a
prolonged and constant systemic absorption. The
rate limiting step for systemic absorption of the
drug substance is usually the permeation through
the epidermis layer. Formulation and product
design influence the permeation of the drug
through the skin, which can be characterized by the
in vitro release of the drug in a dissolution medium
and also by the in vitro permeation through the
human/ animal skin. Physiochemical and biological

International Journal of Pharmaceutical Sciences and Research 1826

Lakhani et al., IJPSR, 2015; Vol. 6(5): 1826-36.
properties of the drug also influence the rate and
extent of transdermal delivery. Such properties
include molecular weight, partition coefficient,
melting point, pKa, solubility and pH effects, as
well as solid state characteristics such as particle
size and polymorphism.
The solution state and solubility of the drug
substance in the drug product should be
determined. The risks of precipitation / particle
growth / change in crystal habit / changes in
thermodynamic activity arising from changes in
temperature and on storage should be assessed and
appropriate tests included in the stability studies.
The drug and the excipients must be compatible
with one another to produce a product that is stable.
This is very significant if the excipients are new.
FIG. 1: HIGHLIGHTS OF VARIOUS ADVANTAGES
OF TRANSDERMAL DRUG DELIVERY SYSTEM.
FIG. 2: FLOWCHART DEPICTING ALL THE
PHYSICOCHEMICAL AND IN VITRO EVALUATION
METHODS.
International Journal of Pharmaceutical Sciences and Research
E-ISSN: 0975-8232; P-ISSN: 2320-5148
Physiochemical Evaluation methods:
Following are the physiochemical evaluation
methods performed for a transdermal patch.
1. Thickness:
As the uniform thickness of the film is desired,
the thickness of the film is measured at three
different places using micrometer, and mean
values were calculated. High-quality Mitutoyo
Digimatic micrometer are widely used for this
purpose7-9.
2. Weight variation:
Weight variation needs to be minimized or
removed among the patches of same batch but
there are always chances of some weight
variation, thus this test gives an idea regarding
weight variation in patches if any. Basically,
five patches are selected randomly and
weighed accurately. The mean was calculated.
The individual weight should not deviate
significantly from the average weight. The
difference in weights of patches gives us an
idea regarding weight variation.
3. Flatness:
The ideal transdermal patch should possess a
smooth surface and should not fold or constrict
with the progress of time. The flatness of a
patchcan be studied by performing the
following test: three longitudinal strips are cut
from each patch i.e. the patch is cut from the
center, left side and right side of the patch thus
covering almost the entire part of patch
surface. The length of each strip should be
measured and minimum deviation is preferred.
The variation in length is measured by
determining percent constriction10,11.
Where, l1 = initial length of each strip,
l2 = final length of each strip.
4. Tensile strength:
Tensile strength instrument or tensiometer can
be used for this purpose. Tensile strength is the
maximum stress applied to a point at which the
specimen breaks. Tensile strength helps
1827
Lakhani et al., IJPSR, 2015; Vol. 6(5): 1826-36.
understand themechanical properties of the
polymeric patches.
The instrument consists of two load cell
groups, the lower one is fixed and the upper
one is movable. The strips (dimension- 2*2
cm) are fixed between these two groups. Force
is gradually applied till the film breaks and the
break force recorded is expressed in kg. Also
elongation can be measured with the help of
pointer mounted on the assembly.
Where, a- width of strip.
b- Thickness of strip.
l- Length of strip.
ΔL- Elongation of patch at break point.
5. Hardness:
Hardness test is performed on three different
patches individually from each batch and
tested by fabricated hardness testing
instrument and the average is calculated.
Hardness is an equally important parameter as
it determines the ability of a patch to take up
mechanical stress, be it during packaging,
transportation or after application.
Hardness apparatus consists of a wooden stand
of 8 cm in height and a top area of 8 x 8 cm. A
hole of 0.2 cm diameter is made in the center
of the wooden top. A small plastic pan is fixed
horizontally on one end of a 2 mm thick
smooth iron rod. Rod having the pan on its
upper end is inserted into the hole of the
wooden top and its lower sharp end was placed
on a metal plate.
Battery of three-volt is widely used to make an
electric circuit. Assembly is set in such way
that, the bulb lights up only when the circuit is
complete via the contact of the metal plate and
the sharp end of the rod.
The patch of interest is placed between the
metal plate and the sharp end of the iron rod
and the weights were gradually added on to the
pan and total weight required to penetrate the
International Journal of Pharmaceutical Sciences and Research
E-ISSN: 0975-8232; P-ISSN: 2320-5148
patch is indicated by the lighted bulb which
was noted as observations10,12.
6. Folding Endurance:
Folding endurance is number of folds required
to break a polymeric patch. This test not only
depicts the strength of the patch prepared using
different polymers, but alsochecks how
efficiently the polymer imparts flexibility.
This test involves a simple phenomenon i.e.
repeatedly fold the same patch at the same
place until it breaks. Thus, the number of times
the patch could be folded at the same place
without breaking/cracking gives us the value
of folding endurance11,13.
7. Drug Content Uniformity:
The transdermal patch of specified area
generally 3.14 cm² is dissolved in 100 ml of
pH 7.4 phosphate buffer. The above solution is
stirred for 2hours was provided to get a
homogeneous solution followed by filtration.
A blank is performed using a drug free patch.
The drug content in each formulation is
determined by measuring the absorbance at a
specific wavelength after suitable dilution
using a UV-visible spectrophotometer10,14.
8. Swellability:
This test is to check the swellability of the
patch due to presence of polymer. This test
requires petri plates and double distilled water,
to see how much the patch would swell upon
contact with water. The patches of 3.14 cm²
are weighed and placed in a petri plates
containing 10 ml of double distilled water and
are allowed to imbibe for specified time.
Increase in weight of the patch is then
determined at specific time intervals until a
constant weight is observed10,15.
The degree of swelling (% S) is calculated
using the formula
Where, S is percent swelling,
Wt is the weight of patch at time t,
Wo is the weight of patch at time zero.
1828
Lakhani et al., IJPSR, 2015; Vol. 6(5): 1826-36.
9. Surface pH:
Surface pH of the patches is described by
Bottenberg et al. The patches are kept in 0.5
ml double distilled water and thus allowed to
swell for 1hour. The surface pH is known by
bringing a combined glass electrode near the
surface of the patch and allowing it to
equilibrate for 1 minute 10, 16.
10. Water vapour transmission:
Quantity of moisture transmitted through a unit
area of a patch in unit time is referred as water
vapour transmission. This in turn helps us to
know the permeation characteristics. Glass
vials of equal dimensions are generally used.
Desiccant (for example, fused calcium
chloride-1gm) is taken in a vial and polymeric
patch is fixed using adhesive. These pre
weighed vial is stored in a humidity chamber
at RH of 80% with the temperature set to 30ºC
for a period of 24 hours. The weight gain is
calculated every hour till a period of 24
hours10, 17.
The water vapour transmission was calculated
using the equation
Where, W is gm of water permeated / 24 hr.
L is thickness of the patch
S is exposed surface area of the patch
11. Skin Irritation Study:
The studies need to be performed firstly on
animals like Rats or Rabbits (Table 1). These
tests give us an idea regarding skin
sensitization or irritation to the formulation.
The patches require direct contact with the
skin, hence the rat’s back is shaved. Following
this it is usually cleaned with distilled water to
remove loose hairs and tissue.
The rats are divided into five groups. Animals
of group I are used as a blank, without any
treatment. The marketed adhesive tape is
applied to one group of animals (Group II,
control). Transdermal systems (blank and drug
loaded) are applied onto the skin of animals of
groups III and IV. A 0.8 % v/v aqueous
International Journal of Pharmaceutical Sciences and Research
E-ISSN: 0975-8232; P-ISSN: 2320-5148
solution of formalin is applied as a standard
irritant (Group V). A new patch is applied to
each group each day up to 7 days and finally
the application sites are graded according to a
scoring scale18.
TABLE 1:DRAIZE SCORING METHOD 19
Skin Reaction
S.No Erythema and Edema Score
Eschar Formation formation assigned
1 No Erythema No edema 0
2 Very slight Erythema Very slight 1
edema
3 Well defined slight edema 2
Erythema
4 Moderate to severe Moderate 3
Erythema edema
5 Severe Erythema Severe slight 4
edema
12. Uniformity of dosage:
A patch should consist of the drug amount
which is necessary to show the desired
activity. The uniformity of dosage in the
patches is checked in this test. A specific area
of the patch is cut into small pieces and
dissolved in a volumetric flask of fixed
capacity post which it is sonicated, volume is
made up, the solution allowed to settle,
following which the supernatant is diluted to a
fixed concentration. This on filtering through a
2um membrane and analysis via HPLC will
give drug content per piece. This test is most
accurate when done in triplets from different
parts, so that we get an average value of
content 10.
13. Polariscope:
The uniform distribution of drug throughout
the patch is necessary to have optimum
activity. The drug accumulation at one site
may create problem during absorption. This
test is involves examination of the drug
crystals in the patch by using a polariscope. A
specific surface area of the piece is to be kept
on the object slide and is observed for the
drugs crystals to distinguish whether the drug
is present as crystalline form or amorphous
form in the patch. The polymorphic form play
important as 2 different forms show different
solubility and hence can show different release
and permeation rates10, 12, 21-23.
1829
Lakhani et al., IJPSR, 2015; Vol. 6(5): 1826-36.
14. Shear Adhesion:
The test signifies the cohesive strength of an
adhesive polymer. A number of factors decide
shear adhesion, such as the molecular weight,
the degree of crosslinking, the composition of
the polymer, its type and the amount of
tackifier added. An adhesive coated tape is
applied onto a stainless steel plate; a specified
weight is hung from the tape, to affect it
pulling in a direction parallel to the plate.
Shear adhesion strength is determined by
measuring the time it takes to pull the tape off
the plate. The longer the time take for removal,
the greater is the shear strength18,12,21-23.
15. Effect on aging:
The effect of progressed time span on the
nature of the patch is studied in this test. The
effect of aging on physical appearance is
studied by packing the polymeric films in
properly sealed aluminium foil and then
storing them in a desiccator at ambient
conditions for 30 days. The patch is then
thoroughly studied for its physical and
physicochemical characterization18,12,21-23.
16. Peel Adhesion test:
The force required to remove an adhesive
coating form a test substrate gives peel
adhesion factor. Molecular weight of adhesive
polymer, the type and amount of additives are
the variables that determine the peel adhesion
properties. A single tape is applied to a
stainless steel plate or a backing membrane of
choice and then the tape is pulled from the
substrate at a 180º angle and the force required
for tape removed is measured. This gives Peel
adhesion rate6,12,21-23.
17. Rolling ball tack test:
In this, Stainless steel ball of 7/16 inches in
diameter is released on an inclined track so
that it rolls down and comes into contact with
the horizontal, upward facing adhesive. The
distance the ball travels along the adhesive
provides the measurement of tack, expressed in
inch6,12, 21-23.
18. Probe Tack test: The Force required to pull a
probe away from an adhesive at a fixed rate is
International Journal of Pharmaceutical Sciences and Research
E-ISSN: 0975-8232; P-ISSN: 2320-5148
recorded as tack. The tip of a clean probe with
a defined surface roughness is brought into
contact with adhesive and when a bond is
formed between probe and adhesive, the
subsequent removal of the probe mechanically
breaks it. The force required to pull the probe
away from the adhesive at fixed rate is
recorded as tack and it is expressed in grams
6,12, 21-23
.
19. Stability and Drug-Polymer Interaction:
The stability of the drug in the patch is
determined by accelerated stability studies as
per the protocol for stability studies in ICH
guidelines. The stable drug can be quantified
using a stability indicating RP-HPLC or other
chromatographic methods. The drug-polymer
interaction can be studied with the help of
differential scanning calorimetry (DSC), X-ray
diffraction technique and FT-IR. The
individual drug polymer peaks can be
compared with that of the mixture. X-ray
diffraction technique also confirms the final
form of the drug in the patch20-23.
20. Texture analyser:
The adhesiveness of the patches is critical in
the drug delivery mechanism, the texture
analyser can be used to quantify the force
required to break the probe surface and
adhesive side of the patch contact by
investigating into the adhesiveness of
transdermal delivery patches by probing with a
ball probe through a holed plate11, 24-26.
FIG. 3: ILLUSTRATION OF TEXTURE ANALYZER.
1830
Lakhani et al., IJPSR, 2015; Vol. 6(5): 1826-36.
Skin permeation In -Vitro Method:
Diffusion Cell permeation test:
Permeation test involves various skin tissues,
whole skin, epidermis or dermis in a specialized
cell also known as “diffusion cell” (Fig) 27. Skin or
tissue is mounted sandwiched between the donor
and the receptor compartment. Drug formulation is
placed in the donor compartment. It is in contact
with tissue on one side and the tissueis in contact
with the receptor solution. The temperature is
controlled throughout the process. The sampling
time points are fixed and the receptor solution is
assayed for the drug 6, 28, 29. Since the skin
membrane is used in between the compartments, it
is essential to find out whether a drug is
immobilized or is it permeating through the skin, if
so then at what rate. The Franz cell can also be
modified by using it directly for drug dissolution
wherein, the skin membrane is replaced by the
transdermal membrane 23, 28.
The various factors affecting the testing
performance 27:
 System Design
 Effect of Temperature
 Effect of Stirring
 Drug Solubility
1) System design:
The primary concernis that method must be able
toput upthe basic system size and type. The
arrangement should be planned such that it too
must be able to fit the system’s theoretical release
pattern. In case the system is to provide burst
release or loading dose, the time intervals of
sampling should be set to specifically, in order to
capture the part of release pattern in addition to the
controlled-release rate portion.
2) Effect of temperature:
The temperature has a significant effect on the
diffusion of drug through the polymer and rate
control membranes. The target temperature is
generally 32/35oC (mimic the temperature on the
surface of the skin). Temperature control is
required throughout the test within the range
±0.3oC for accurate and precise measurement of the
rate. Temperature effect will be prominent for the
controlled portion rather than the burst portion.
International Journal of Pharmaceutical Sciences and Research
E-ISSN: 0975-8232; P-ISSN: 2320-5148
Stirrer
Sample Port
Donor Compartmet Receptor Compartment
Skin mounted between
donor and receptor
compartment
FIG. 4: DIFFUSION CELL.
3) Effect of Stirring:
Diffusion dependent controlled release of the
system is directly relative to ‘Apparent
concentration’ at the system-receptor solution
interface. Poor stirring leads to building up of the
concentration gradient at the interface, leading to
reduced diffusional drug flow. Too high stirring
rates will be futile.
4) Drug Solubility:
Release of the drugfrom donor to receptor
compartment is affected directly by the drug in the
receptor solution in general and at the system-
solution interface in particular. The drug release is
affected by “percent saturation” (also known as
activity) in the system and the receptor solution.
The difference in concentration (concentration
gradient) is driving force for diffusion. The release
mechanism are best predicted when we can limit
drug concentration in the solution to less than 10%
saturation (sink condition). For hydrophobic drug/
drug with low solubility, their solubility can be
improved by adding a surfactant or organic solvent
to receptor compartment. However, it may cause to
increase the release rate or modify diffusion
coefficients of the drug in the membranes.
Therefore, the easiest way to limit saturation effects
is to use larger volumes or shorter collection
intervals to maintain sink condition.
In-Vitro Dissolution Methods:
The USP 30 has three official apparatuses (5, 6 and
7). The whole system for dissolution study needs to
1831
Lakhani et al., IJPSR, 2015; Vol. 6(5): 1826-36.
have a larger receptor solution volumes that can
meet saturation-limit requirements. Therefore,
diffusion cells are not the apparatus of choice.
Collection format is a characteristic feature. It is
either cumulative, flow through or interval.
In the cumulative collection format we collect the
released drug in a single container. For example
apparatus 5 and 6. Apparatus 5 (Fig. 5) is referred
to as “paddle over disk” and 6 (Fig.7) utilizes a
spinning cylinder to stir the system. Drug
concentration increases in vessel in a cumulative
manner. Apparatus 6 uses the same system as
apparatus 1, except the basket is replaced with the
“cylinder stirring element”. The transdermal is
attached to the circumference of the cylinder with
the help of a water-permeable occlusive
Cuprophan. Cuprophan is inert porous cellulose
material.
FIG. 5: USP 23 APPARATUS 51.
Flow through/interval systems (USP apparatus 7)
have small “cell volumes” and controlled flow of
receptor solution is used through cell to collect the
drug. Drug solution can either be measured in
flowing solution or from a well-stirred collection
vessel. The main advantage of this format is that
the fresh receptor solution in constantly in the
contact with donor solution. Interval collection
involves collecting the drug released in a series of
receptor solutions, each indexed at particular
intervals, USP apparatus 7 27 ,30.
A. Paddle over disc (type 5):
 In - vitro drug release studies:
International Journal of Pharmaceutical Sciences and Research
E-ISSN: 0975-8232; P-ISSN: 2320-5148
This type of apparatus is used to study the In Vitro
drug release kinetics of transdermal patches. It is
also knows as a USP type V apparatus. The main
components of the system are a basket, a paddle
and a glass slide which is used to support the
prepared film.
The film that is to be studied is taken and a specific
portion of it is cut. The dimensions of the cut are
fixed and noted as they will be later required during
the calculation of drug release. The adhesive part of
the patch is attached onto the glass slide which is
placed in the basket. This is followed by the
addition of the 500mL of the dissolution medium or
phosphate buffer at pH 7.4.
The temperature of the medium is set to 32± 0.5°C
and the paddle is placed at a distance of 2.5mm
from the surface of the membrane. The paddle is
run at 50 rpm. The samples (5mL) can be drawn at
fixed time intervals up to 24 hrs. The drawn sample
must be replaced with an equal quantity of the
dissolution media. Data obtained from this would
be more accurate when done in triplicates 31.
Alternatively, the patch can be compressed
between a glass slide and a mesh 32 and used in a
type 2 dissolution apparatus, by placing the above
“sandwich” at the base of the basket. The sandwich
can be held by using either Plastic 33 or binder clips
34
.
 In vitro skin permeation studies:
This process can be done in one of two ways with
reference to the membrane used. It can either be
done using the abdominal skin of Male Wistar Rats
31
or using Human abdominal Skin 29.
In case of Human abdominal skin, first, the
adipose tissue is removed via blunt dissection. This
is followed by the immersion of the epidermis in
water at 60°C for 1 min, which causes it to separate
35
. This is followed by careful removal of the
epidermis and then preserving it by storing it at -
20°C. Before performing the experiment, the
epidermis is defrosted carefully followed by cutting
sections of the desired size for use. It is placed in
the Franz Diffusion cell after the receptor
compartment is filled with the desired media. Once
the donor compartment is filled, it is covered by a
1832
Lakhani et al., IJPSR, 2015; Vol. 6(5): 1826-36. E-ISSN: 0975-8232; P-ISSN: 2320-5148

backing membrane in order to prevent loss of the
reservoir solution or membrane dehydration. In this
case it is essential to maintain the receptor
compartments temperature at 37°C.
In case of Wistar Rats (weighing 200-250gm), the
hair from the abdominal skin must be carefully
removed, followed by thorough cleaning of the skin
(dermal surface) with distilled water. It is now
equilibrated in either the dissolution medium or
phosphate buffer of pH 7.4 for one hour. If the
fluids are stirred during this process, it helps
achieve better equilibration. In this case, the
temperature is maintained at 32 ± 0.5°C using a
thermostatically controlled heater.
Once equilibrated, the Rats skin is placed between
the donor and receptor compartments. The
remaining procedure is repeated as done with
Human abdominal skin. The receptor
compartments dissolution media should be
replenished after each sample withdrawal. Samples
are to be filtered before UV or HPLC analysis.31, 36.
B. Apparatus 6 (Rotating Cylinder Method):
This is similar to the above apparatus, except the
basket and the shaft/stirrer are replaced with a
stainless steel cylinder and shaft. This apparatus is
designed as per the specifications in FIG. 5: USP 23
APPARATUS 5. The dosage to be tested is placed
in the cylinder and the shaft is arranged at a distance
of 25± 2 mm during the test. The required volume
of dissolution fluid is added and the temperature is
maintained at 32 ± 0.5°C.
cylinder) where as in the actual design, and the
membrane is stagnant. Thus, it is not an exact
mimic of the actual system. Furthermore, the
rotation may cause the membrane to release more
drag than it actually would since a larger surface
area is in contact with the mobile fluid.
TABLE 2: ACCEPTANCE CRITERIA 1.
Level Number Criteria
Tested
L1 6 No individual value lies outside the
stated range
L2 6 The average value of the 12 units
(L1+L2) lies within the stated
range. No individual value is
outside the stated range by more
than 10% of the average of the
stated range
L3 12 The average value of the 24 units
(L1+L2+L3) lies within the stated
range.Not more than 2 of the 24
units are the stated range by more
than 10% of the average of the
stated range , and none of the units
is outside the stated range by more
than 20% of the average of the
stated range
Patch glued
FIG. 6: APPARATUS 6 ROD WITH CYLINDER

The membranes adhesive surface is applied to a

piece of cuprophan, following which it is dried for 1
min. This is followed by attaching the adhesive part
of cuprophan base (with the membrane attached to
its non-adhesive part) to the cylinder along its outer
circumference (FIG. 7). The cylinder can now be
placed in the apparatus and is rotated at the desired
rate. Samples are withdrawn at the fixed time
intervals from the space between the upper rotating
portion of the cylinder and the surface of the
dissolution fluid but not less than 1cm from the wall
37
.

This system is less preferred over Type 5 since in

this, the membrane is in motion (spins on the FIG. 7 USP APPARATUS 6 1.

International Journal of Pharmaceutical Sciences and Research 1833

Lakhani et al., IJPSR, 2015; Vol. 6(5): 1826-36. E-ISSN: 0975-8232; P-ISSN: 2320-5148

and when 50 and 85% of the drug has been

released. Refer to Table 1 for quantities of active
ingredients expected to be released, unless
specified otherwise.

FIG 8: DIFFERENT USP APPARATUS TYPES 38

C. USP Type 7:
The vessels (previously calibrated) used in this are
either made of glass or any suitable inert material.
It also has a a motor and drive assembly which
helps the machine to automatically reciprocate the
system vertically and also allows it to index the
system horizontally to a different to a different
row of vessels and suitable sample holders.
FIG.9: USP TYPE 6 1

The containers are partially immersed in a water

CONCLUSION: A number of In vitro techniques
bath. This apparatus must be operated in a
are available both to analyze the physical and
disturbance (physical) free room and on a stable
chemical properties of the patch and also to
platform. The size container and sample holder are
analyze/ mimic its behavior in real time conditions.
used as specified in the individual monograph. 37
These tests help us further understand how altering
the excepients or any of the physical properties of
The sample is attached by cyano-acrylate glue to a
the patch can affect the drug release from the patch
sample holder, followed by which the system is
in real time conditions. Further research needs to be
pressed onto a dry piece of cuprophan. The
focused on a customized platform that can be used
cuprophan must be pressed on order to remove
as a standard to deliver any drug for transdermal
entrapped air. This in turn is attached to a sample
use.
holder containing an O-ring. Now the back of the
sample membrane is attached to the base of the
ACKNOWLEDGEMENTS: We would like to
holder and its frontal part is exposed to the
thank the BITS Pilani Hyderabad for giving us the
solution. This entire arrangement is attached to a
environment to learn about and work on
suitable sample holder as per the specified
Transdermal Delivery patches. We would
monograph.
additionally like to thank our Professor, Dr. Punna
Rao Ravi and our H.O.D Dr. Shrikanth Charde for
In Vitro Release Criteria— the time points chosen
their help and support.
should record drug release at 1 hour of dissolution

International Journal of Pharmaceutical Sciences and Research 1834

Lakhani et al., IJPSR, 2015; Vol. 6(5): 1826-36.
REFERENCES:
1. Revision USPCCo. United States Pharmacopeia and
National Formulary. United States Pharmacopeial
Convention, Incorporated; 1994.
2. Swarbrick J. Encyclopedia of Pharmaceutical
Technology. Vol 2. Third edition ed: Informa
healthcare; 2006.
3. Chien YW. Development of transdermal drug delivery
systems. Drug Development and Industrial Pharmacy.
1987; 13(4-5):589-651.
4. Prausnitz MR, Langer R. Transdermal drug delivery.
Nature biotechnology. 2008; 26(11):1261-1268.
5. Saroha K, Yadav B, Sharma B. Transdermal patch: A
discrete dosage form. International Journal of Current
Pharmaceutical Research. 2011; 3(3):98-108.
6. Dhiman S, Singh TG, Rehni AK. Transdermal patches:
A recent approch to new drug delivery system. Int J
Pharm Pharm Sci. 2011; 3(5):26-34.
7. Parthasarathy G, Reddy KB, Prasanth V. Formulation
and characterization of transdermal patches of naproxen
with various polymers. Pharmacie Globale (IJCP).
2011; 2(6):1-3.
8. Bharkatiya M, Nema R, Bhatnagar M. Designing and
characterization of drug free patches for transdermal
application. International Journal of Pharmaceutical
Sciences and drug research. 2010; 2(1):35-39.
9. Amnuaikit C, Ikeuchi I, Ogawara K-i, Higaki K,
Kimura T. Skin permeation of propranolol from
polymeric film containing terpene enhancers for
transdermal use. International journal of pharmaceutics.
2005; 289(1):167-178.
10. Guideline on Quality of Transdermal Patches. European
Medicines Agency. 2012(EMA/CHMP/ QWP/911254/
2011).
11. Sharma A, Saini S, Rana A. Transdermal drug delivery
system: a review. SKIN. 2012; 4(15):18-19.
12. Seth A, Agarwal G, Saini T. Evaluation of free films.
Indian drugs. 1985; 23(1):45-46.
13. Patel NA, Patel NJ, Patel RP. Design and evaluation of
transdermal drug delivery system for curcumin as an
anti-inflammatory drug. Drug development and
industrial pharmacy. 2009; 35(2):234-242.
14. Bharkatiya M, Nema RK, Bhatnagar M. Development
and characterization of transdermal patches of
metoprolol tartrate. Development. 2010; 3(2).
15. Peh KK, Wong CF. Polymeric films as vehicle for
buccal delivery: swelling, mechanical, and bioadhesive
properties. J Pharm Pharm Sci. 1999; 2(2):53-61.
16. Bottenberg P, Cleymaet R, Muynck C, et al.
Development and testing of bioadhesive,
fluoride‐containing slow‐release tablets for oral use.
Journal of pharmacy and pharmacology. 1991;
43(7):457-464.
17. Crawford R, Esmerian O. Effect of plasticizers on some
physical properties of cellulose acetate phthalate films.
Journal of pharmaceutical sciences. 1971; 60(2):312-
314.
18. Darwhekar G, Chaurasia S. Formulation Development
and Evaluation of Transdermal Patches of Losartan.
2012.
19. Draize JH, Woodard G, Calvery HO. Methods for the
study of irritation and toxicity of substances applied
topically to the skin and mucous membranes. Journal of
International Journal of Pharmaceutical Sciences and Research
E-ISSN: 0975-8232; P-ISSN: 2320-5148
pharmacology and Experimental Therapeutics. 1944;
82(3):377-390.
20. Prasad Verma P, Chandak A. Development of matrix
controlled transdermal delivery systems of pentazocine:
In vitro/in vivo performance. Acta pharmaceutica.
2009; 59(2):171-186.
21. Aqil M, Ali A, Sultana Y, Najmi A. Fabrication and
evaluation of polymeric films for transdermal delivery
of pinacidil. Die Pharmazie-An International Journal of
Pharmaceutical Sciences. 2004; 59(8):631-635.
22. Agrawal SS, Pruthi JK. Development and evaluation of
matrix type transdermal patch of ethinylestradiol and
medroxyprogesterone acetate for anti-implantation
activity in female Wistar rats. Contraception. 2011;
84(5):533-538.
23. McCrudden MT, Alkilani AZ, McCrudden CM, et al.
Design and physicochemical characterisation of novel
dissolving polymeric microneedle arrays for
transdermal delivery of high dose, low molecular
weight drugs. Journal of Controlled Release. 2014;
180:71-80.
24. Singh TP, Singh RK, Shah JN, Mehta TA.
Mucoadhesive Bilayer Buccal Patches Of Verapamil
Hydrochloride: Formulation Development And
Characterization.
25. Brown M, Jones SA. Hyaluronic acid: a unique topical
vehicle for the localized delivery of drugs to the skin.
Journal of the European Academy of Dermatology and
Venereology. 2005; 19(3):308-318.
26. Chien Y. Novel drug delivery systems. Informa Health
Care; 1991.
27. Chaisson D. Dissolution testing of transdermal systems.
Dissolution Technologies. 1995; 2(1):7-11.
28. Suksaeree J, Boonme P, Taweepreda W, Ritthidej GC,
Pichayakorn W. Characterization,in vitro release and
permeation studies of nicotine transdermal patches
prepared from deproteinized natural rubber latex
blends. Chemical Engineering Research and Design.
2012; 90(7):906-914.
29. Silva NH, Rodrigues AF, Almeida IF, et al. Bacterial
cellulose membranes as transdermal delivery systems
for diclofenac: In vitro dissolution and permeation
studies. Carbohydrate polymers. 2014; 106:264-269.
30. Ming M, Connie C, Lee PH, Broman CT, Cleary GW.
New improved paddle method for determining the in
vitro drug release profiles of transdermal delivery
systems. Journal of controlled release. 1993; 27(1):59-
68.
31. Bijaya G, Preethi G, Roopak M, Versha P. Transdermal
delivery of ibuprofen and its prodrugs by passive
diffusion and Iontophoresis. International Journal of
Pharmacy and Pharmaceutical Sciences. 2010; 2(1):79-
85.
32. Shah VP, Tymes NW, Yamamoto LA, Skelly JP. In
vitro dissolution profile of transdermal nitroglycerin
patches using paddle method. International journal of
pharmaceutics. 1986; 32(2):243-250.
33. Knepp VM, Hadgraft J, Guy R. Transdermal drug
delivery: problems and possibilities. Critical reviews in
therapeutic drug carrier systems. 1986; 4(1):13-37.
34. Chien YW. Transdermal Controlled Systemic
Medications: International Pharmaceutical R & D
Symposium on Advances in Transdermal Controlled
1835
Lakhani et al., IJPSR, 2015; Vol. 6(5): 1826-36. E-ISSN: 0975-8232; P-ISSN: 2320-5148

Drug Administration for Systemic Mediations: Papers. 37. Clarence T. Ueda VPS, Kris, Derdzinski GE, Gordon
Dekker; 1987. Flynn, Howard Maibach, Margareth Marques, Howard
35. Kligman AM, Christophers E. Preparation of isolated Rytting, Steve Shaw, Kailas Thakker, and Avi Yacobi.
sheets of human stratum corneum. Archives of Topical and Transdermal Drug Products. Dissolution
Dermatology. 1963; 88(6):702-705. Technologies. 2010; 17(4):12-25.
36. Rajesh N, Gowda D, Somasheka R. Formulation And 38. Brahmankar D, Jaiswal SB. Biopharmaceutics and
Evaluation of Biopolymer Based Transdermal Drug pharmacokinetics: A treatise. Vallabh prakashan; 2005.
Delivery. International Journal of Pharmacy &
Pharmaceutical Sciences. 2010; 2.
How to cite this article:
Lakhani P, Bahl R and Bafna P: Transdermal Patches: Physiochemical and in-vitro Evaluation Methods. Int J Pharm Sci Res 2015; 6(5):
1826-36.doi: 10.13040/IJPSR.0975-8232.6(5).1826-36.

All © 2013 are reserved by International Journal of Pharmaceutical Sciences and Research. This Journal licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 3.0 Unported License.

This article can be downloaded to ANDROID OS based mobile. Scan QR Code using Code/Bar Scanner from your mobile. (Scanners are
available on Google Playstore)

International Journal of Pharmaceutical Sciences and Research 1836